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Stem
A 34-year-old woman presents to the clinic with a 4-month history of weight loss (8 kg despite an increased appetite), heat intolerance, palpitations, a fine tremor, anxiety and increasingly frequent loose stools. Her periods have become irregular. She is a non-smoker. On examination: pulse 112/min irregularly irregular, BP 142/68, warm moist palms, a fine tremor of the outstretched hands, lid lag, brisk reflexes, and a diffusely enlarged, smooth, non-tender thyroid with an audible systolic bruit. There is bilateral proptosis with chemosis. Investigations: TSH under 0.05 mIU/L (0.4 to 4.0), free T4 48 pmol/L (10 to 20), free T3 16 pmol/L (3.5 to 6.5).
Questions
a) What is the most likely diagnosis and the two key investigations to confirm the cause? (2 marks) Graves disease (TSH-receptor stimulating antibody, TRAb) — supported by the diffuse goitre with a bruit and the Graves orbitopathy (proptosis, chemosis). Confirm with (1) TSH receptor antibody (TRAb/TSI) — positive in Graves — and (2) a thyroid uptake scan showing diffuse high uptake (low uptake would indicate thyroiditis/factitious).
b) List four clinical features in the stem that distinguish Graves from toxic multinodular goitre and thyroiditis. (3 marks)
- Diffuse, smooth goitre with a bruit — the hypervascularity of Graves; TMNG is nodular and thyroiditis is tender/painless without a bruit.
- Graves orbitopathy (proptosis, chemosis) — pathognomonic for Graves; never in TMNG, adenoma, or thyroiditis.
- Weight loss with an INCREASED appetite (thyrotoxic hypermetabolism) plus a smooth (not nodular) gland.
- Non-tender gland — excludes subacute (de Quervain) thyroiditis, which is painful and tender with a raised ESR.
c) Outline the definitive treatment options and recommend a first-line therapy with drug, dose and duration. (3 marks) Three definitive options: (1) antithyroid drugs (carbimazole/methimazole), (2) radioactive iodine (I-131), (3) surgery (thyroidectomy). First-line for this young Graves patient: carbimazole 20 to 30 mg daily (titration regimen), reducing to a maintenance of 5 to 15 mg daily once euthyroid, continued for 12 to 18 months (remission in 40 to 50%). Add propranolol 20 to 40 mg every 6 to 8 hours for symptom control. Counsel her on the agranulocytosis warning: any sore throat, fever or mouth ulcer — stop the drug and get an urgent full blood count.
d) Two months later she is admitted confused, febrile (39.8 degrees C) and in rapid atrial fibrillation. What is the diagnosis and outline the immediate management in the correct pharmacological order? (2 marks) Thyroid storm (thyrotoxic crisis), precipitated by non-adherence or intercurrent illness. Management bundle, applied simultaneously:
- Supportive: oxygen, IV fluids, cooling with paracetamol (NOT aspirin — displaces T4/T3 from TBG), ICU.
- Thionamide FIRST — PTU 500 to 1000 mg loading then 250 mg every 4 hours (preferred in storm — inhibits TPO AND D1 deiodinase).
- Iodine (Lugol's or SSKI) ONE HOUR AFTER the thionamide — Wolff-Chaikoff effect; never before.
- Propranolol (IV esmolol if unstable) for tachyarrhythmia; hydrocortisone 100 mg IV every 8 hours; treat the precipitant (cultures, antibiotics).
Stem C teaching (pregnancy — short SAQ add-on)
e) How does management change if she is 8 weeks pregnant? (bonus 2 marks)
- Confirm thyrotoxicosis with free T4/T3; TRAb for Graves.
- Avoid radioactive iodine entirely in pregnancy and for months before conception planning.
- Antithyroid drug: many centres use PTU in first trimester (methimazole/carbimazole embryopathy risk), then switch to carbimazole/methimazole later to reduce PTU hepatotoxicity — follow current ATA/local guidance.
- Beta-blocker short-term only (fetal growth concerns with prolonged use).
- Surgery (second trimester) reserved for intolerance/failure/compression; lowest effective thionamide dose (fetal hypothyroidism risk).